PROJECT SUMMARY Sensorineural hearing loss (SNHL) is the most common form of permanent hearing loss, often caused by cumulative exposure to loud sounds. Individuals with SNHL have a well-known reduced sensitivity to sound, but lesser-known are the deficits in the abilities to both localize sound sources and use binaural cues to aid sound source detectability and intelligibility in noisy environments. Most mammals, including humans, localize the azimuth (horizontal position) of sound sources by identifying differences in the intensity and arrival time of sound waves at the two ears, known as interaural level and time differences (ILD and ITD), respectively. Neural sensitivity to ITD and ILD first arises in auditory brainstem nuclei that project to the central nucleus of the inferior colliculus (IC). The purpose of the project is to determine the effect of SNHL on the neural representation of sound source azimuth in the central nucleus of the IC. A model of SNHL will be developed in Dutch-belted rabbits, a species with a comparable audiogram to humans. SNHL will be induced in rabbits under anesthesia via overexposure to loud noise. Changes in cochlear function will be quantified by measuring the post-exposure shift in threshold sound level necessary to evoke either the auditory brainstem response (ABR), whose earliest component arises from the auditory nerve, or distortion product otoacoustic emissions (DPOAE), which are related to cochlear outer hair cell function. Threshold shifts in ABRs and DPOAEs will be compared to post- exposure changes in the number of inner and outer hair cells in the cochlea, measured with immunofluorescent labeling under a confocal microscope. Sound-evoked responses of single neurons in the central nucleus of the IC will be measured in and compared between awake rabbits with or without noise-induced SNHL. The sensitivity of each neuron will be measured to sound source frequency, level, azimuth (ITD and ILD co-varying together) and ITD alone. The information about sound source azimuth transmitted by IC neurons will be computed using information-theoretic and population decoding analyses. IC neurons from rabbits with SNHL are predicted to transmit less information about sound source azimuth than those of normal-hearing rabbits. Mechanisms of potential disruption of binaural coding in the IC will be investigated using signal processing models of the IC based on known effects of SNHL on auditory nerve fiber responses.